Various anaerobic microorganisms, including Succinivibrio dextrinosolvens, Fibrobacter succinogenes, Ruminococcus flavefacienis and the like, produce succinic acid as an end product by glucose metabolism (Zeikus, Annu. Rev. Microbiol., 34:423, 1980). Strains that produce succinic acid at industrially useful yield have not yet been reported except for Anaerobiospirillum succiniciproducens known to produce succinic acid at high concentration and high yield from glucose upon the presence of excessive CO2 (David et al., Int. J Syst. Bacteriol., 26:498, 1976). However, since Anaerobiospirillum succiniciproducens is an obligate anaerobic microorganism, a fermentation process of producing succinic acid using this microorganism has a shortcoming that the process itself becomes unstable even upon exposure to a very small amount of oxygen.
To overcome this shortcoming, Mannheimia succiniciproducens 55E was developed that is a strain having not only resistance to oxygen but also high organic acid productivity. However, since this strain produces formic acid, acetic acid and lactic acid in addition to succinic acid, it has shortcomings in that it has low yield and costs a great deal in a purification process of removing other organic acids except succinic acid.
Recombinant E. coli strains for the production of succinic acid have been reported in various literatures. If the E. coli strains have disruptions of a gene coding for lactate dehydrogenase and a gene coding for pyruvate formate-lyase, it is hard for them to grow in anaerobic conditions. Furthermore, they have too low yield to apply them to industrial field, since, although lactic acid is not produced as a fermentation product, other metabolites (acetic acid and ethanol) account for about half of the production of succinic acid. In an attempt to overcome such shortcomings, E. coli cells were grown in aerobic conditions, and then anaerobic conditions were applied to induce the fermentation of succinic acid. However, this attempt still has low productivity (Vemuri et al., J. Ind. Microbiol. Biotechnol., 28:325, 2002). Also, other examples were reported in which the genes of enzymes, such as pyruvate carboxylase, phosphoenolpyruvate carboxylase, phosphoenolpyruvate carboxykinase, and malic enzyme, that immobilize CO2 in a metabolic pathway of succinic acid fermentation, are introduced into E. coli, thereby increasing the production of succinic acid (Vemuri et al., Appl. Environ. Microbiol., 68:1715, 2002; Millard et al., Appl. Environ. Microbiol., 62:1808, 1996; Chao and Liao, Appl. Environ. Microbiol., 59:4261, 1993; Stols and Donnelly, Appl. Environ. Microbiol., 63:2695, 1997).
Meanwhile, it is known that the disruption of ptsG in E. coli contributes to an improvement of bacterial production and succinic acid production (Chatterjee et al., Appl. Environ. Microbiol., 67:148. 2001), but most of rumen bacteria have no ptsG, and thus have an advantage that they do not require a removal process of ptsG as in the case of E. coli. Recently, an attempt is actively conducted in which the genes of enzymes that immobilize CO2 in a metabolic pathway of succinic acid fermentation are introduced into rumen bacteria, including genus Actinobacillus and genus Anaerobiospirillum. However, in this attempt, other organic acids were produced at large amounts or the yield of succinic acid was so low, as a result of that, it did not reach an industrially applicable level.